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A novel microRNA-based strategy to expand the differentiation potency of stem cells
by
Álvarez-Fernández, Monica
, Clark, Susan J
, Zhong, Cuiqing
, Muñoz, Jaime
, Serrano, Manuel
, Izpisua Belmonte, Juan Carlos
, Trakala, Marianna
, Zapatero-Solana, Elisabet
, Yang, Yu
, Valdés-Mora, Fátima
, Bueno, María José
, Serrano, Rosa
, Abad, María
, Osvaldo Graña Castro
, Blasco, María A
, Salazar-Roa, Maria
, Marta Gómez De Cedrón
, Malumbres, Marcos
, Peters, Timothy J
, Da-Zhi, Wang
, Fernández-Piqueras, José
, Ortega, Sagrario
in
Cardiomyocytes
/ Cell Biology
/ Cell differentiation
/ Cell self-renewal
/ Chimerism
/ Complementation
/ Deoxyribonucleic acid
/ Developmental stages
/ DNA
/ DNA methylation
/ Heart
/ MicroRNAs
/ miRNA
/ Pluripotency
/ Regenerative medicine
/ Stem cell transplantation
/ Stem cells
2019
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A novel microRNA-based strategy to expand the differentiation potency of stem cells
by
Álvarez-Fernández, Monica
, Clark, Susan J
, Zhong, Cuiqing
, Muñoz, Jaime
, Serrano, Manuel
, Izpisua Belmonte, Juan Carlos
, Trakala, Marianna
, Zapatero-Solana, Elisabet
, Yang, Yu
, Valdés-Mora, Fátima
, Bueno, María José
, Serrano, Rosa
, Abad, María
, Osvaldo Graña Castro
, Blasco, María A
, Salazar-Roa, Maria
, Marta Gómez De Cedrón
, Malumbres, Marcos
, Peters, Timothy J
, Da-Zhi, Wang
, Fernández-Piqueras, José
, Ortega, Sagrario
in
Cardiomyocytes
/ Cell Biology
/ Cell differentiation
/ Cell self-renewal
/ Chimerism
/ Complementation
/ Deoxyribonucleic acid
/ Developmental stages
/ DNA
/ DNA methylation
/ Heart
/ MicroRNAs
/ miRNA
/ Pluripotency
/ Regenerative medicine
/ Stem cell transplantation
/ Stem cells
2019
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Do you wish to request the book?
A novel microRNA-based strategy to expand the differentiation potency of stem cells
by
Álvarez-Fernández, Monica
, Clark, Susan J
, Zhong, Cuiqing
, Muñoz, Jaime
, Serrano, Manuel
, Izpisua Belmonte, Juan Carlos
, Trakala, Marianna
, Zapatero-Solana, Elisabet
, Yang, Yu
, Valdés-Mora, Fátima
, Bueno, María José
, Serrano, Rosa
, Abad, María
, Osvaldo Graña Castro
, Blasco, María A
, Salazar-Roa, Maria
, Marta Gómez De Cedrón
, Malumbres, Marcos
, Peters, Timothy J
, Da-Zhi, Wang
, Fernández-Piqueras, José
, Ortega, Sagrario
in
Cardiomyocytes
/ Cell Biology
/ Cell differentiation
/ Cell self-renewal
/ Chimerism
/ Complementation
/ Deoxyribonucleic acid
/ Developmental stages
/ DNA
/ DNA methylation
/ Heart
/ MicroRNAs
/ miRNA
/ Pluripotency
/ Regenerative medicine
/ Stem cell transplantation
/ Stem cells
2019
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A novel microRNA-based strategy to expand the differentiation potency of stem cells
Paper
A novel microRNA-based strategy to expand the differentiation potency of stem cells
2019
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Overview
Full differentiation potential along with self-renewal capacity is a major property of pluripotent stem cells (PSCs). However, the differentiation capacity frequently decreases during expansion of PSCs in vitro. We show here that transient exposure to a single microRNA, expressed at early stages during normal development, improves the differentiation capacity of already-established murine and human PSCs. Short exposure to miR-203 in PSCs (miPSCs) results in expanded differentiation potency as well as improved efficiency in stringent assays such as tetraploid complementation and human-mouse interspecies chimerism. Mechanistically, these effects are mediated by direct repression of de novo DNA methyltransferases Dnmt3a and Dnmt3b, leading to transient and reversible erasing of DNA methylation. As a proof of concept, miR-203 improves differentiation and maturation of PSCs into cardiomyocytes in vitro as well as cardiac regeneration in vivo, after cardiac injury. These data support the use of transient exposure to miR-203 as a general and single method to reset the epigenetic memory in PSCs, and improve their use in regenerative medicine. Footnotes * Supplemental files added.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
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